Alzheimer's Allele Related to Early Beta-Amyloid Deposition

Article excerpt

Cerebrospinal fluid levels of amyloid-beta 42 may be a biomarker for the early, asymptomatic phase of Alzheimer's disease--a long-awaited leap forward in the quest for preclinical diagnosis, reported Dr. Elaine R. Peskind of the University of Washington, Seattle, and her associates.

Adults who carry the apolipoprotein E4 allele but are cognitively normal show a marked decline in cerebrospinal fluid (CSF) levels of amyloid-beta 42 (A[[beta].sub.42]), presumably because the protein is precipitating out of the CSF and being deposited in plaques within the brain parenchyma, Dr. Peskind and her colleagues noted.

This decline of A[[beta].sub.42] in cerebrospinal fluid appears to begin in early adulthood and to rapidly accelerate between the ages of 50 and 60 years in apo E4 carriers, long before the clinical manifestations of Alzheimer's disease (AD) appear. The finding bolsters the theory that A[[beta].sub.42] deposition in the brain is a key initiating factor in the pathogenesis of AD, the researchers reported. The findings may also point the way to new therapies (Arch. Neurol. 2006;63:936-9).

Dr. Peskind and her associates assessed both the apo E genotype and CSF concentrations of A[[beta].sub.42] in 184 healthy adults aged 21-88 years. The 94 men and 90 women had normal cognition and function.

Those found to have the apo E allele not only had lower levels of A[[beta].sub.42], but their levels also declined in a linear fashion as age increased. CSF levels also dropped off precipitously between the ages of 50 and 60 years. In contrast, subjects who did not carry the apo E4 allele showed a slight rise in A[[beta]. …